There has been an increased interest in speech pattern analysis applications of Parkinsonism for building predictive telediagnosis and telemonitoring models. For this purpose, we have collected a wide variety of voice samples, including sustained vowels, words, and sentences compiled from a set of speaking exercises for people with Parkinson's disease. There are two main issues in learning from such a dataset that consists of multiple speech recordings per subject: 1) How predictive these various types, e.g., sustained vowels versus words, of voice samples are in Parkinson's disease (PD) diagnosis? 2) How well the central tendency and dispersion metrics serve as representatives of all sample recordings of a subject? In this paper, investigating our Parkinson dataset using well-known machine learning tools, as reported in the literature, sustained vowels are found to carry more PD-discriminative information. We have also found that rather than using each voice recording of each subject as an independent data sample, representing the samples of a subject with central tendency and dispersion metrics improves generalization of the predictive model.

• Clinical examination is important for diagnosis of carpal tunnel syndrome • Shear wave elastography (SWE) offers new clinical opportunities within diagnostic ultrasound • SWE is highly reproducible in evaluation of median nerve stiffness • Median nerve stiffness is significantly increased in carpal tunnel syndrome • Elastography could become useful in diagnosis of carpal tunnel syndrome.

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific deubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1 GLU7ALA ), shared by all affected subjects. As demonstrated by isothermal titration calorimetry, purified UCHL1 GLU7ALA , compared with WT, exhibited at least sevenfold reduced affinity for ubiquitin. In vitro, the mutation led to a near complete loss of UCHL1 hydrolase activity. The GLU7ALA variant is predicted to interfere with the substrate binding by restricting the proper positioning of the substrate for tunneling underneath the cross-over loop spanning the catalytic cleft of UCHL1. This interference with substrate binding, combined with near complete loss of hydrolase activity, resulted in a >100-fold reduction in the efficiency of UCHL1 GLU7ALA relative to WT. These findings demonstrate a broad requirement of UCHL1 in the maintenance of the nervous system. protein quality control | recessive inherited neurodegeneration

Purpose To evaluate the value of shear-wave elastography (SWE) in the detection of diabetic peripheral neuropathy (DPN) of the tibial nerve. Materials and Methods This study was approved by the institutional review board, and written informed consent was obtained from all study participants. The study included 20 diabetic patients with DPN (10 men, 10 women), 20 diabetic patients without DPN (eight men, 12 women), and 20 healthy control subjects (nine men, 11 women). The tibial nerve was examined at 4 cm proximal to the medial malleolus with gray-scale ultrasonography and SWE. The nerve cross-sectional area (in square centimeters) and the mean nerve stiffness (in kilopascals) within the range of the image were recorded. Inter- and intrareader variability, differences among groups, and correlation of clinical and electrophysiologic evaluation were assessed with intraclass correlation coefficients, the Mann Whitney U test, and the Wilcoxon signed rank test. Results Between diabetic patients with and diabetic patients without DPN, mean age (60 years [range, 38-79 years] vs 61 years [range, 46-75 years], respectively), mean duration of diabetes (10 years [range, 1-25 years] vs 10 years [range, 2-26 years]), and mean body mass index (31.4 kg/m [range, 24.7-48.1 kg/m] vs 29.8 kg/m [range, 22.9-44.0 kg/m]) were not significantly different. Diabetic patients without DPN had significantly higher stiffness values on the right side compared with control subjects (P < .001). Patients with DPN had much higher stiffness values on both sides compared with both diabetic patients without DPN (P < .001) and healthy control subjects (P < .001). A cutoff value of 51.0 kPa at 4 cm proximal to the medial malleolus revealed a sensitivity of 90% (95% confidence interval [CI]: 75.4%, 96.7%) and a specificity of 85.0% (95% CI: 74.9%, 91.7%). Conclusion Tibial nerve stiffness measurements appear to be highly specific in the diagnosis of established DPN. The increased stiffness in subjects without DPN might indicate that the nerve is affected by diabetes. RSNA, 2016 Online supplemental material is available for this article.

BACKGROUND AND PURPOSE: SWI is a new technique for evaluating diffuse axonal injury associated with punctate hemorrhages. The aim of our study was to determine the prevalence of cerebral microhemorrhages in amateur boxers compared with nonboxers by using SWI and to evaluate the sensitivity of SWI compared with T2 FSE and T2*GE sequences.